Hypothalamopituitary adrenal (HPA) axis dysfunction occurs frequently in patients with major depression. The relationship of HPA dysfunction to the development of depressive symptomatology remains an enigma. The proposed study is to determine the significance of HPA axis abnormalities in major depression. The study tests the hypothesis that hypercortisolemia is related to the occurrence of cognitive impairment and cerebral atrophy in depression. Cognitive impairment is measured using a computerized cognitive neuromotor test battery and by paper and pencil tasks. The tasks chosen for this battery are those known to the affected by glucocorticoids. Cerebral atrophy and other neuroanatomical/physico chemical changes are assessed using Magnetic Resonance Imaging (MRI). Twenty four hour urine free cortisol and nocturnal multiple time point cortisol and the dexamethasone suppression test sampling are used as indices of hypercortisolemia. In addition, the study will examine the relationship between adrenocortical hyperplasia as measured by computerized tomography of the adrenal gland, measures @of HPA function, cognitive impairment and changes on MRI. The relationship ;between reversibility of HPA function and cognitive changes, MRI changes and adrenocortical hyperplasia will also be assessed. These studies will provide a better understanding of the pathophysiology of hypercortisolemia in depression and may lead to novel management approaches in the .prevention and treatment of depression. These studies will also lead to a more comprehensive and definitive knowledge about the nature and severity of cognitive deficits and neuroanatomical changes in patients with depression. They will also advance our understanding of the neurobiological basis of cognitive dysfunction in depression and the psychobiology of stress.